Linked Life Data

9699501

Source:http://linkedlifedata.com/resource/pubmed/id/9699501

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1998-8-21
pubmed:abstractText
Bone sialoprotein (BSP), a secreted glycoprotein found in bone matrix, has been implicated in the formation of mammary microcalcifications and osteotropic metastasis of human breast cancer (HBC). BSP possesses an integrin-binding RGD (Arg-Gly-Asp) domain, which may promote interactions between HBC cells and bone extracellular matrix. Purified BSP, recombinant human BSP fragments and BSP-derived RGD peptides are shown to elicit migratory, adhesive, and proliferative responses in the MDA-MB-231 HBC cell line. Recombinant BSP fragment analysis localized a significant component of these activities to the RGD domain of the protein, and synthetic RGD peptides with BSP flanking sequences (BSP-RGD) also conferred these responses. The fibronectin-derived RGD counterpart, GRGDSP (Gly-Arg-Gly-Asp-Ser-Pro), could not support these cellular responses, emphasizing specificity of the BSP configuration. Although most of the proliferative and adhesive responses could be attributed to RGD interactions, these interactions were only partly responsible for the migrational responses. Experiments with integrin-blocking antibodies demonstrated that BSP-RGD-induced migration utilizes the alpha(v)beta3 vitronectin receptor, whereas adhesion and proliferation responses were alpha(v)beta5-mediated. Using fluorescence activated cell sorting, we selected two separate subpopulations of MDA-MB-231 cells enriched for alpha(v)beta3 or alpha(v)beta5 respectively. Although some expression of the alternate alpha(v) integrin was still retained, the alpha(v)beta5-enriched MDA-MB-231 cells showed enhanced proliferative and adhesive responses, whereas the alpha(v)beta3-enriched subpopulation was suppressed for proliferation and adhesion, but showed enhanced migratory responses to BSP-RGD. In addition, similar analysis of two other HBC cell lines showed less marked, but similar RGD-dependent trends in adhesion and proliferation to the BSP fragments. Collectively, these data demonstrate BSP effects on proliferative, migratory, and adhesive functions in HBC cells and that the RGD-mediated component differentially employs alpha(v)beta3 and alpha(v)beta5 integrin receptors.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal, http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, http://linkedlifedata.com/resource/pubmed/chemical/IBSP protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Integrin-Binding Sialoprotein, http://linkedlifedata.com/resource/pubmed/chemical/Integrins, http://linkedlifedata.com/resource/pubmed/chemical/Oligopeptides, http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Vitronectin, http://linkedlifedata.com/resource/pubmed/chemical/Sialoglycoproteins, http://linkedlifedata.com/resource/pubmed/chemical/arginyl-glycyl-aspartic acid, http://linkedlifedata.com/resource/pubmed/chemical/integrin alphaVbeta5
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9541
pubmed:author
pubmed:issnType
Print
pubmed:volume
176
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
482-94
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Bone sialoprotein supports breast cancer cell adhesion proliferation and migration through differential usage of the alpha(v)beta3 and alpha(v)beta5 integrins.
pubmed:affiliation
Department of Cell Biology, Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.